Age-dependent determinants of infectious complications profile in children and adults after hematopoietic cell transplantation: lesson from the nationwide study

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IntroductionLeukemia belong to 31% of all childhood malignancies. Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric leukemia accounting for 80–85% of all cases. Progress in diagnostics and therapy of leukemia is dependent on international cooperation. The objective of the study was the analysis of non-hematological toxicity during intensive chemotherapy according to two consecutive intercontinental protocols.Patients and methodsA total number of 210 children diagnosed for ALL who were treated in single center between 2002 and 2018 were divided in two groups defined by therapeutic protocol: ALL IC-BFM 2002 (group 1) and ALL IC-BFM 2009 (group 2). Data were entered prospectively from 2002 into international ALL IC-BFM 2002 and ALL IC-BFM 2009 registry. Non-hematological toxicity was analyzed according to the criteria followed in protocols, compatible with CTCAE criteria.ResultsThe most frequent toxicities included hepatic toxicity with transaminitis and hyperbilirubinemia, infections, oral mucositis and gut toxicity with vomiting, and/or diarrhea. Non-hematological toxicity episodes calculated as a ratio per patient were comparably often observed in both the groups; however, the distribution was different. There were more grade III and less grade II toxicities. This was mainly related to significant increase in the rates of infections and transaminitis. However, there was a significant decrease in vomiting and central and peripheral neurotoxicity.ConclusionsIntensive treatment of ALL is burdened with frequent severe toxic and infectious complications. Further progress in therapy of pediatric ALL is dependent on sophisticated supportive therapy and very well experienced and knowledgeable therapeutic team.

Section: Discussionmentioning

confidence: 99%

Acute non-hematological toxicity of intensive chemotherapy of acute lymphoblastic leukemia in children

Demidowicz

Bartoszewicz

Czyżewski

et al. 2020

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“…This project was widened to include the adult hematopoietic transplant setting for the period 2012-2014. The overall results of this national project were presented elsewhere [8,9,10].…”

Section: Design Of the Studymentioning

confidence: 99%

“…Organization for the Research and Treatment of Cancer/ Mycosis Study Group (EORTC/MSG) as proven, probable, or possible in the 2002 and 2008 versions, and finally revised and updated according to the new 2019 criteria[11]. All HCT and PHO patients were screened with the galactomannan test mainly during neutropenia or on the basis of clinically driven indications[8,9,10].…”

mentioning

confidence: 99%

Clinical spectrum and outcome of invasive mucormycosis in children and adults: Polish experience of the decade 2010–2019

Styczyński

Czyżewski

Frączkiewicz

et al. 2020

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No epidemiological data exist so far on invasive mucormycosis (IM) in Polish hematopoietic cell transplantation (HCT) and pediatric hemato-oncology (PHO) centers. The objective of this study was to analyze the incidence, clinical course, therapy, and outcome of IM in pediatric and adult patients undergoing HCT and children with hemato-oncological diseases in Poland. A total number of 12425 at-risk patients were retrospectively analyzed, and the period between 2010 and 2019 was included. Patients were analyzed in three groups: nontransplant children with malignancies, children undergoing HCT, and adults after HCT. Twenty-one patients were diagnosed with IM, including 15 children (10 non-HCT, 5 HCT) and 6 HCT adults. Proven IM was confirmed in 18 patients, probable in 2 patients, and possible in 1 patient. Proven IM was diagnosed in 7.1% of all patients with invasive fungal diseases (IFDs), including 8.1% among PHO patients, 5.4% among pediatric HCT patients, and 7.0% among adult HCT patients. Clinically, pneumonia was diagnosed in 10 (47.6%) patients, involvement of the paranasal sinuses was found in 3 (14.3%) patients, gastrointestinal disease was noted in 2 (9.5%) patients, and disseminated mucormycosis was found in 6 (28.6%) patients. The probability of overall survival in IM patients was 0.50 ± 0.11. Infection-related mortality (IRM) was 10% for pediatric nontransplant IM patients and 82% for transplant IM (pediatric + adult) patients (p = 0.004). Among the transplant patients, all adults died within 120 days. IRM for pediatric HCT patients was 60% (p = 0.038). The only prognostic factor was HCT, which adversely influenced survival in IM patients.

“…No child died of infection after auto-HCT. In multivariate analysis, the risk factors for death from infection were following: adult vs children, diagnosis of acute leukemia, mismatched transplants, chronic GVHD, infection with Gram-negative bacteria, CMV reactivation, and also duration of infection >21 days [27].…”

Section: Children Versus Adults: Infections Are More Frequent and Havmentioning

confidence: 99%

Infectious complications in children and adults with hematological malignancies

Styczyński

2019

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Infections are the main cause of morbidity and mortality in pediatric hematology and oncology (PHO) and hematopoietic cell transplantation (HCT) settings in children and adults. The analysis of incidence and outcome of bacterial, fungal, and viral infections in Polish PHO/ HCT centers was performed over a period of 72 months (2012–2017). The summary of infections in 5628 patients with newly diagnosed malignancy and 971 HCTs is presented in this paper. Additionally, data of 650 pediatric HCTs from 2012 to 2015 were compared with the data of 3200 HCTs in adults. The risk of any infection per patient was higher in HCT vs PHO patients (2062/971 vs 7115/5628; 2.1 vs 1.3; HR=1.7, p<0.0001). The incidence of bacterial infections was 34,2±0,6% in PHO vs 41,5±1,6% in HCT patients, and the outcome was better in PHO patients: 97,9±0,2% vs 91,8±1,0%. The incidence of patients with fungal infection was 8,8±0,4% vs 21,2±1,3%, and the outcome was better in PHO patients: 95,9±0,7% vs 85,8±2,3%. Incidence of viral infections was 5,0±1,0% in PHO setting, including part of previously transplanted patients, and 47,8±2,2% in HCT setting (60,9±2,3% allo-HCT; 5,6±1,3% auto-HCT). In children, the incidence was higher for bacterial (36.0% vs 27.6%), fungal (25.3% vs 6.3%), and viral (56.3% vs 29.3% allo-HCT; 6.6% vs 0.8% auto-HCT) infections than in adults (p<0.0001), and the outcome was better for bacterial (95.5% vs 91.4%), fungal (88.0% vs 74.9%), and viral (98.6% vs 92.3%) infections. In conclusion, the presented large studies have determined the incidence of infectious complications and their outcomes in HCT and PHO centers in Poland.